Lipoproteins in fasting plasma comprise three primary fractions: the very low density (VLDL) fraction, the low density (LDL) fraction, and the high density (HDL) fraction. It has been observed that a high VLDL+LDL:HDL ratio is associated with a correspondingly high incidence of premature coronary artery disease. ("The Low Density Lipoprotein Pathway and its Relation to Atherisochlerosis", J. L. Goldstein, and M. S. Brown 1977. Annual Review of Biochemistry 46:897-930). Furthermore, an inverse relation has been observed between a high HDL:VLDL+LDL ratio and total mortality due to cardiovascular disease. ("Associations of Serum High Density Lipoprotein and Total Chloesterol with Total Cardiovascular and Cancer Mortality in a Seven Year Prospective Study of 10,000 Men.", S. Yaari, U. Goldbourt, S. Ivan-Zohar and H. W. Nerifeld 1981. Lancet 1:1011-1015).
It is known in the art that lipoproteins can be removed selectively from blood plasma or serum by the use of a sulphated ion exchanger. In U.S. Pat. No. 4,096,136 dated June 20, 1978 there is described an in vitro treatment of blood serum of plasma for selective removal of lipoprotein fractions for analytical purposes. Lipoproteins are selectively bound in the presence of other plasma or serum proteins and ions. The process involves the equilibration of the sulphated ion exchanger in a column with a solution containing a divalent cation, and the addition of the same cation to the plasma or serum to adjust the divalent cation concentration of the plasma or serum to between 0.05 and 1.0M. The plasma or serum is then passed through the equilibrated column where the the lipoproteins are selectively bound and the other components remain in the plasma or serum. The bound lipoproteins are eluted from the column and the proportion of LDL, VLDL and HDL is determined. The greater the proportional amount of the LDL and VLDL, the more a patient is at risk.
The method of U.S. Pat. No. 4,096,136 is an analytical one. It would be desirable to be able to extract selectively the LDL and VLDL fraction while leaving the HDL in plasma or serum and then reuse the plasma or serum. The process of U.S. Pat. No. 4,096,136 is not physiologically acceptable because of the inherent toxicity of the divalent cation used in the first step. Any blood so treated would be physiologically incompatible.
It has now unexpectedly been found that by employing a sulphated ion exchanger having a relatively high degree of substitution it is possible to bind the LDL and VLDL fractions without the use of a relatively high concentration of divalent cations in the equilibrating solution. In addition HDL is not retained, thus use of the column allows maximum adjustment of the HDL:LDL+VLDL ratio.
It is an object of this invention to go some way toward achieving this desideratum, or at least to offer the public a useful choice.